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Zika virus infection: An overview

Zika virus infection: An overview
Author:
A Desiree LaBeaud, MD, MS
Section Editor:
Martin S Hirsch, MD
Deputy Editor:
Keri K Hall, MD, MS
Literature review current through: Jan 2024.
This topic last updated: Dec 08, 2023.

INTRODUCTION — Zika virus is an arthropod-borne flavivirus transmitted by mosquitoes [1-6]. The virus is related to other flaviviruses including dengue virus, yellow fever virus, and West Nile virus. Clinical manifestations of Zika virus infection occur in approximately 20 percent of patients and include acute onset of low-grade fever with maculopapular pruritic rash, arthralgia (notably small joints of hands and feet), or conjunctivitis (nonpurulent).

Neurotropism of Zika virus has been demonstrated in vivo and in vitro [7-11]. Zika virus infection has been associated with neurologic complications; these include congenital microcephaly (in addition to other developmental problems among babies born to women infected during pregnancy), Guillain-Barré syndrome, myelitis, and meningoencephalitis [12-14]. (See 'Complications' below.)

Online updates regarding Zika virus infection may be viewed at the following websites:

●Pan American Health Organization/World Health Organization website

●United States Centers for Disease Control and Prevention website

●European Centre for Disease Prevention and Control website

General issues related to Zika virus epidemiology, clinical manifestations, and prevention are reviewed here. Issues related to Zika virus infection in pregnant women and infants with congenital exposure are discussed separately. (See "Zika virus infection: Evaluation and management of pregnant patients" and "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate".)

EPIDEMIOLOGY

Geographic distribution — Outbreaks of Zika virus infection have occurred in Africa, Southeast Asia, the Pacific Islands, the Americas, and the Caribbean. In 2015 and 2016, a Zika virus outbreak occurred in the Americas, the Caribbean, and the Pacific [15-17]. Updates regarding the geographic distribution of Zika virus may be viewed at the United States Centers for Disease Control and Prevention website and the Pan American Health Organization/World Health Organization website.

Zika virus is named after the Ugandan forest where it was first isolated from a rhesus monkey in 1947 [18]. The first human cases were detected in 1952 in Uganda and Tanzania. The virus subsequently spread across equatorial Africa and Asia, where it was associated with sporadic infections. The first major recognized outbreak occurred in the Yap Islands of Micronesia in 2007; more than 70 percent of the population ≥3 years of age was infected, resulting in an estimated 5000 infections among the total population of 6700 [19-21]. Another larger outbreak occurred in French Polynesia in 2013 to 2014, which affected about two-thirds of the population, resulting in approximately 32,000 infections [22,23]. During the outbreak in French Polynesia, 3 percent of donated blood samples tested positive for Zika virus by polymerase chain reaction [24].

Zika virus infections were first detected in the Western hemisphere in February 2014 on Chile's Easter Island [25]. Zika virus infections were subsequently detected in Brazil in May 2015 [25,26]. Molecular analyses have suggested that the virus may have been introduced earlier, in late 2013 or early 2014 [27]. Regions with mosquito-borne transmission of Zika virus are summarized below. (See 'Travel advisories for pregnant women' below.)

In the United States in 2016, there were 5168 confirmed or probable cases of noncongenital Zika virus disease [28-30]. Mosquito-borne transmission has occurred in Florida and Texas, and imported Zika infection has been reported in travelers [31-35]. In one report from New York City including 3605 individuals with travel-associated exposure who underwent Zika virus laboratory testing between January and June 2016, positive results were observed in 182 patients (5 percent of cases), including 20 pregnant women [36]. The first case of Zika-related congenital microcephaly in the United States was reported in January 2016 in Hawaii in a baby born to a woman who had resided in Brazil during her pregnancy [37]. The first case of sexually transmitted Zika virus infection in the United States was reported in Texas in February 2016 [38].

Travel advisories for pregnant women — Given an association between Zika virus exposure during pregnancy and congenital microcephaly, a number of authorities have advised that pregnant women avoid or consider postponing travel to areas below 6500 feet (2000 meters) where mosquito transmission of Zika virus is ongoing [39-44]. Regions above 6500 feet (2000 meters) are excluded from travel precautions, since the mosquitoes that transmit Zika virus are rare in these locations and the risk for mosquito-borne transmission of Zika virus is minimal [44].

Countries and territories with local mosquito-borne transmission of Zika virus may be reviewed on the website maintained by the United States Centers for Disease Control and Prevention (CDC).

Within the continental United States, mosquito-borne transmission of Zika virus infection has occurred in Florida and Texas; guidance for pregnant women may be found on the CDC website [45,46]

Transmission — Zika virus may be transmitted to humans via the following [24,38,47-57]:

●Bite of an infected mosquito

●Maternal-fetal transmission

●Sex (including vaginal, anal, and oral sex)

●Blood product transfusion

●Organ transplantation

●Laboratory exposure

Preventive measures based on the various modes of transmission are discussed below. (See 'Prevention' below.)

The primary mode of transmission is via mosquito bites. Zika virus is carried by the Aedes aegypti mosquito, which lives in tropical regions; however, the Aedes albopictus mosquito, which lives in temperate regions, is also capable of carrying it (figure 1 and figure 2) [58-60]. Aedes mosquitoes can also transmit dengue and chikungunya viruses. (See 'Mosquito protection' below.)

Zika virus RNA has been detected in blood, urine, semen, saliva, female genital tract secretions, cerebrospinal fluid, amniotic fluid, and breast milk [24,61-71]:

●Blood – In nonpregnant individuals with Zika virus infection, Zika virus RNA is usually detectable in the serum for about two weeks [71]; Zika virus RNA is detectable in whole blood as late as 81 days following onset of illness [72,73]. In pregnancy, Zika virus RNA has been detected in the serum as late as 107 days after onset of illness [74-76].

●Urine – Zika virus RNA usually clears from urine after about six weeks [71]; Zika virus RNA has been detected in urine up to 91 days after onset of illness [63,66,67,77-79]. Replicating virus has been detected in urine at the time of symptomatic illness [80].

●Semen – Zika virus RNA can be detected in semen when no longer detectable in blood. Zika virus RNA usually clears from semen after about three months [71,81], but has been detected in semen up to 188 days after onset of illness [67,79,82-86].

However, molecular test results may not fully reflect the likelihood of transmissibility. In a prospective study including 184 men with symptomatic Zika virus infection, Zika virus RNA persisted in the semen of some men for more than six months; however, Zika virus RNA-positive semen samples were infectious (as demonstrated by cell culture and plaque assay) in only 4 percent of cases [87]. Cell culture infectivity was observed only in samples obtained within 30 days after illness onset with viral load >7.0 log RNA copies per milliliter of semen.

●Sexual transmission of Zika virus as late as 41 days after a partner's onset of symptoms has been described [49,88]. Infectious Zika virus in semen (detected via culture) has been detected as late as 69 days after onset of illness [89].

●Female genital tract secretions – Zika virus RNA has been detected in female genital tract secretions (via endocervical swabs and cervical mucus) during symptomatic illness [68]. Zika virus RNA has also been detected in cervical mucus 14 days after onset of illness, when it was no longer detectable in blood or urine [54,68,73].

●Saliva – Zika virus RNA has been detected in saliva up to 91 days after onset of illness [64,67,79]. Replicating virus has been detected in saliva at the time of symptomatic illness [80].

●Tears – Zika virus RNA has been detected in tears up to 30 days after onset of illness [90].

In one description of shedding dynamics in adults, Zika virus RNA was detected in plasma, urine, and saliva of 57, 93, and 69 percent of participants; estimated median times to clearance were 11, 24, and 14 days, respectively. Zika virus RNA was detected in the semen of 5 of 10 tested men; the median time to clearance was 25 days, and the longest duration of shedding in semen was 370 days [91].

Human-to-human transmission apart from sexual transmission has been described [92,93]. The mechanism of such transmission is uncertain; in the reports described, close contact occurred while the index patient's viral load was very high, and it is possible that body fluids (such as sweat or tears) of patients with Zika virus disease could be infectious.

Issues related to maternal-fetal transmission and breastfeeding are discussed separately. (See "Zika virus infection: Evaluation and management of pregnant patients", section on 'Congenital infection'.)

CLINICAL MANIFESTATIONS — The incubation period between mosquito bite and onset of clinical manifestations is typically 2 to 14 days [94]. The illness is usually mild; symptoms resolve within two to seven days. Immunity to reinfection occurs following primary infection [94]. Severe disease requiring hospitalization is uncommon, and case-fatality rates are low [95-99].

Prior dengue infection may be protective against symptomatic Zika virus infection [100]; further study is needed [100].

Symptoms and signs

Adults — Clinical manifestations of Zika virus infection occur in 20 to 25 percent of individuals who become infected with Zika virus [101,102]. Symptomatic infection has been described more frequently among women and patients <40 years in one study; however, neither female sex nor age was associated with an increased prevalence of infection [103].

Symptoms and signs of Zika virus infection typically include acute onset of low-grade fever (37.8 to 38.5°C), pruritic rash (erythematous macules and papules may be present on the face, trunk, extremities, palms, and soles), arthralgia (notably in the small joints of the hands and feet), and conjunctivitis (nonpurulent); clinical illness is consistent with Zika virus disease if two or more of these symptoms are present [104-108]. Other commonly reported clinical manifestations include myalgia, headache, dysesthesia, retro-orbital pain, and asthenia [104-108]. Relapse of symptoms in the absence of repeat exposure has been described [109].

Less commonly observed symptoms and signs include abdominal pain, nausea, diarrhea, and mucous membrane ulcerations [106,107,110]. Thrombocytopenia has been observed and may be attributable to an immune-mediated mechanism [111]. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis", section on 'Inciting events'.)

Other manifestations including facial puffiness, palatal petechiae, uveitis, transient hearing impairment, myocarditis, and pericarditis have been described in case reports [73,112-123].

Clinical manifestations of Zika virus infection among organ transplant recipients has been described in a small series including four patients [124]. The patients presented with abnormal graft function, thrombocytopenia (<100,000/mm3), and bacterial superinfection; two had fever and myalgia. No rash, conjunctivitis, or neurologic symptoms were observed.

Children — The range of Zika virus infection in children includes intrauterine infection (vertical transmission during pregnancy), intrapartum infection (vertical transmission at the time of delivery), and postnatal infection (transmission via mosquito bites). Issues related to intrauterine and intrapartum infection are discussed separately. (See "Zika virus infection: Evaluation and management of pregnant patients" and "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate".)

Clinical manifestations in infants and children with postnatal infection are similar to the findings seen in adults with Zika virus infection [20,125-130]. Arthralgia is difficult to detect in infants and young children and may manifest as irritability, walking with a limp, difficulty moving or refusing to move an extremity, pain on palpation, or pain with active or passive movement of the affected joint [125]. (See "Evaluation of the child with joint pain and/or swelling".)

Thus far, no developmental complications have been observed in otherwise healthy children with postnatal Zika virus infection [131-133]. However, such children may be at risk for neurologic abnormalities, including a higher rate of epilepsy [134,135]. (See 'Other neurologic complications' below.)

Prior exposure to Zika virus may worsen the presentation of dengue disease [136].

Complications — Zika virus infection has been associated with complications including congenital microcephaly and fetal losses among women infected during pregnancy, as well as neurologic complications. Issues related to congenital infection are discussed separately. (See "Zika virus infection: Evaluation and management of pregnant patients" and "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate".)

Guillain-Barré syndrome — There have been several descriptions of Guillain-Barré syndrome (GBS) in association with Zika virus infection [26,137-150]:

●A retrospective study in Colombia evaluated 68 patients with GBS between fall 2015 and spring 2016, 97 percent of whom had symptoms of Zika virus infection within one month prior to onset of GBS symptoms [139]. Of 37 patients tested with serology, 86 percent had evidence of recent flavivirus infection; of 42 patients tested with reverse-transcription polymerase chain reaction (RT-PCR), 40 percent had positive results. Among those tested with nerve-conduction studies and electromyography, 78 percent had the acute inflammatory demyelinating polyneuropathy subtype of GBS. Intensive care was required for 59 percent of patients, and four died.

●A case-control study in French Polynesia evaluated the association between GBS and Zika virus infection during the 2013 to 2014 outbreak [141]. Cases included 42 patients diagnosed with GBS; one control group included 98 patients with nonfebrile illnesses (matched for age, sex, and residence), and a second control group included 70 patients with Zika virus infection in the absence of neurologic complications. Zika immunoglobulin (Ig)M was positive in 93 percent of GBS cases (versus 17 percent of patients in the first control group); serologic evidence of past dengue infection was similar among all three groups. Anti-glycolipid IgG antibodies were detected in fewer than 50 percent of GBS cases, raising the possibility of direct viral neurotoxicity. Results of nerve conduction studies were consistent with the acute motor axonal neuropathy type of GBS; clinical improvement during follow-up suggested reversible conduction failure. Symptoms of Zika virus infection occurred in 88 percent of patients with GBS; the median interval between viral syndrome and onset of neurologic symptoms was six days. All GBS cases received intravenous immune globulin, 38 percent required intensive care, and 29 percent needed respiratory care; all survived. The incidence of GBS during the outbreak was estimated to be 2.4 cases per 10,000 Zika virus infections.

In general, the risk for GBS (from any cause) appears to increase with age. GBS is more common in adults and in males; however, individuals of all ages can be affected [151].

Issues related to diagnosis, evaluation, and management of Guillain-Barré syndrome are discussed further separately. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis" and "Guillain-Barré syndrome in adults: Treatment and prognosis".)

Other neurologic complications — Zika virus has been associated with other complications including [97,145,152-157]:

●Encephalitis

●Transverse myelitis

●Encephalomyelitis

●Meningoencephalitis

●Chronic inflammatory demyelinating polyneuropathy

●Brain ischemia

●Neuropsychiatric and cognitive symptoms

These entities are discussed further separately. (See "Viral encephalitis in adults" and "Transverse myelitis: Etiology, clinical features, and diagnosis" and "Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis".)

Effect on fertility — The relationship between Zika virus infection and fertility is a topic of ongoing investigation [158]. Zika virus has been detected in semen and female genital tract secretions. (See 'Transmission' above.)

One study including 15 men with Zika virus infection noted that average sperm counts dropped between day 7 and day 30 following infection (from 119 million to 45 million); the counts generally normalized by day 120 following infection [159].

DIAGNOSIS — The approach to Zika virus diagnosis may vary depending on available resources; the approach outlined in the following sections may need to be tailored to local circumstances.

The diagnosis of Zika virus infection should be suspected in individuals with typical clinical manifestations and relevant epidemiologic exposure (residence in or travel to an area where mosquito-borne transmission of Zika virus infection has been reported, or unprotected sexual contact with a person who meets these criteria). Case definitions for Zika virus infection may be found on the United States Centers for Disease Control and Prevention (CDC) website.

Issues related to diagnosis of Zika virus infection in nonpregnant adults and children with postnatal infection are discussed below. Issues related to diagnosis of Zika virus infection in pregnant women and infants with possible intrauterine Zika virus exposure are discussed separately. (See "Zika virus infection: Evaluation and management of pregnant patients" and "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate".)

Symptomatic adults — The diagnosis of Zika virus infection is definitively established via real-time reverse-transcription polymerase chain reaction (rRT-PCR) for Zika virus RNA (in serum, urine, or whole blood) or Zika virus serology [39,160-168]. Serum and urine are the primary diagnostic specimens; whole blood is an approved specimen for some nucleic acid assays.

There are limited data that indicate Zika virus RNA may persist longer in urine and whole blood than in serum [78,169]; providers should confirm acceptable sample types with the testing laboratory. For all diagnostic testing conducted on specimen types other than serum, it is also necessary to obtain a concurrent serum specimen for reflex IgM testing.

The diagnostic approach depends on the timing of clinical presentation as follows:

●For individuals presenting ≤7 days after onset of symptoms, rRT-PCR of serum (or whole blood) and urine for detection of Zika virus RNA should be performed (algorithm 1) [160]. Any positive rRT-PCR result establishes a diagnosis of Zika virus infection and in such cases no further testing is indicated. Negative rRT-PCR results do not exclude Zika virus infection and should prompt Zika virus serologic testing (Zika virus IgM and plaque reduction neutralization test [PRNT]).

If Zika virus IgM tests results are positive, equivocal, or inconclusive, testing for neutralization antibodies via PRNT should be performed to determine whether the Zika virus IgM reflects recent Zika virus infection or a false-positive result. A PRNT titer greater than 10 should be interpreted as evidence of infection with a specific flavivirus when the PRNT to the other viruses tested is less than 10 (table 1) [160]. However, PRNT may not be adequate to distinguish between Zika and dengue infection, and for this reason the CDC has advised against its use in Puerto Rico [168].

Testing for dengue virus infection and chikungunya virus infection should also be pursued (unless there is no history of residence in or travel to an area where mosquito-borne transmission of Zika virus infection has been reported, and the only potential epidemiologic exposure is unprotected sexual contact with a person who meets these criteria) (algorithm 1) [160,170].

A single RT-PCR test is available through the CDC and other qualified laboratories to evaluate for presence of Zika, chikungunya, or dengue infection [171].

All serologic results should be interpreted with caution since there can be cross-reactivity with other flaviviruses (such as dengue virus). Cross-reactivity may also be observed in individuals who have been vaccinated against yellow fever or Japanese encephalitis [172]. Issues related to diagnosis of dengue virus and chikungunya virus are discussed further separately. (See "Dengue virus infection: Clinical manifestations and diagnosis" and "Chikungunya fever: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

●For individuals presenting >7 days after onset of symptoms, diagnostic testing for Zika virus infection should consist of Zika virus serologic testing (Zika virus IgM and PRNT) (algorithm 1) [160].

Previous flavivirus infection can alter Zika virus diagnostic test characteristics: in one study, Zika virus nonstructural protein 1 (NS1)-specific IgM antibodies were undetectable in patients with previous dengue; among flavivirus-naive patients, the median times to detection of NS1 IgM and IgG antibodies were 8 and 17 days, respectively [91].

Laboratory testing for Zika virus infection is performed by the Pan American Health Organization/World Health Organization, the CDC Arboviral Diagnostic Laboratory, and some state health departments. In the United States, state health departments should be contacted to facilitate diagnostic testing for Zika virus infection. Laboratory specimens may also be sent to the CDC Arboviral Diagnostic Laboratory; instructions are available online. Communication should be initiated with the laboratory via telephone (1-970-221-6400) prior to shipment of specimens.

The US Food and Drug Administration has authorized use of commercial Zika virus serum polymerase chain reaction testing and serologic testing by qualified laboratories [173,174]. Commercial laboratories performing rRT-PCR do not routinely perform Zika IgM enzyme-linked immunosorbent assay (ELISA) or confirmatory serologic testing (PRNT) [175]. Therefore, if possible, providers should store a serum aliquot in a refrigerator (2 to 8°C) for subsequent Zika IgM ELISA testing if the rRT-PCR assay is negative; otherwise, collection of an additional serum sample may be necessary.

A United States commercial testing facility, Laboratory Corporation of America (LabCorp), has reported some false-positive results with a Zika virus IgM ELISA (manufactured by InBios International); it is unclear whether the results are related to the assay or to the commercial testing facility [176]. Positive Zika IgM results are only presumptive for detection of antibodies to Zika virus; confirmation requires additional testing by the CDC.

Symptomatic children with postnatal infection — Postnatal Zika virus infection (eg, transmitted via mosquito bites) should be suspected in an infant or child with relevant epidemiologic exposure in the last two weeks and ≥2 of the following manifestations: fever, rash, conjunctivitis, or arthralgia [125,130]. (See 'Children' above.)

The diagnostic approach for these children is the same as for adults, as described above. (See 'Symptomatic adults' above.)

Asymptomatic individuals — There is no role for Zika virus testing in asymptomatic individuals who are not pregnant. Issues related to diagnosis of Zika virus in asymptomatic pregnant women are discussed separately. (See "Zika virus infection: Evaluation and management of pregnant patients".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of Zika virus infection includes:

●Other viral causes of arthritis:

•Dengue fever – Dengue virus and Zika virus infections have similar clinical manifestations and are transmitted by the same mosquito vector. However, dengue infection usually presents with high fever, severe muscle pain, and headache and may also be associated with hemorrhage; unlike Zika infection, dengue is typically not associated with conjunctivitis (table 2). Coinfection with Zika, chikungunya, and dengue viruses has been described [177,178]. The diagnosis of dengue virus infection is established via serology or reverse-transcription polymerase chain reaction (RT-PCR) (table 1 and algorithm 1) [160]. (See "Dengue virus infection: Clinical manifestations and diagnosis".)

•Chikungunya – Chikungunya virus and Zika virus cause similar symptoms and signs and are transmitted by the same mosquito vector. However, chikungunya usually presents with high fever and intense joint pain affecting the hands, feet, knees, and back; unlike Zika infection, chikungunya is typically not associated with conjunctivitis (table 2). Chikungunya infection can be disabling, causing patients to bend over such that they cannot walk, and infected individuals may be unable to perform simple manual tasks. Coinfection with Zika, chikungunya, and dengue viruses has been described [177-179]. The diagnosis of chikungunya virus infection is established via serology or RT-PCR. (See "Chikungunya fever: Epidemiology, clinical manifestations, and diagnosis".)

•Parvovirus – Parvovirus infection can present with acute and symmetric arthritis or arthralgia, most frequently involving the small joints of the hands, wrists, knees, and feet. Rash may or may not be present. The diagnosis is established via serology. (See "Clinical manifestations and diagnosis of parvovirus B19 infection".)

•Rubella – Clinical manifestations of rubella include low-grade fever and coryza. Macular rash begins on the face and spreads to the trunk, and arthritis and lymphadenopathy may be present. The diagnosis is established via serology. (See "Rubella".)

•A number of other viruses including enterovirus, adenovirus, and alphaviruses may also cause arthritis; these are discussed further separately. (See "Viral arthritis: Causes and approach to evaluation and management".)

●Measles – Clinical manifestations of measles include fever, cough, sore throat, coryza, conjunctivitis, and lymphadenitis. Koplik spots may precede the generalized rash. The diagnosis is established via serology. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention".)

●Leptospirosis – Leptospirosis is characterized by fever, rigors, myalgia, conjunctival suffusion, and headache. Less common symptoms and signs include cough, nausea, vomiting, diarrhea, abdominal pain, and arthralgia. It may be distinguished from Zika virus infection by the presence of jaundice. The diagnosis is established via serology. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Malaria – Malaria is characterized by fever, malaise, nausea, vomiting, abdominal pain, diarrhea, myalgia, and anemia. The diagnosis of malaria is established by visualization of parasites on peripheral smear. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children".)

●Rickettsial infection – Rickettsial infections with similar manifestations as Zika virus infection include African tick bite fever and relapsing fever. African tick bite fever is observed among travelers to Africa and the Caribbean and is characterized by headache, fever, myalgia, solitary or multiple eschars with regional lymphadenopathy, and generalized rash; the diagnosis is established via serology. Relapsing fever is characterized by fever, headache, neck stiffness, arthralgia, myalgia, and nausea; diagnostic tools include direct smear and polymerase chain reaction. (See "Other spotted fever group rickettsial infections" and "Clinical features, diagnosis, and management of relapsing fever".)

●Group A Streptococcus – Clinical manifestations of group A Streptococcus infection include fever, myalgia, cutaneous manifestations (cellulitis, fasciitis), pharyngitis, and shock. The diagnosis established by positive cultures from the blood or other tissues. (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".)

MANAGEMENT — There is no specific treatment for Zika virus infection. Management consists of rest and symptomatic treatment, including drinking fluids to prevent dehydration and administration of acetaminophen to relieve fever and pain [180].

Management of thrombocytopenia related to Zika virus infection is discussed separately [111]. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis", section on 'Inciting events'.)

Aspirin and other nonsteroidal anti-inflammatory drugs should be avoided until dengue infection has been ruled out, to reduce the risk of hemorrhage. Aspirin should not be used in children with acute viral illness because of its association with Reye syndrome. (See "Acute toxic-metabolic encephalopathy in children", section on 'Reye syndrome'.)

The World Health Organization has issued initial guidance on psychosocial support for patients and families affected by Zika virus infection and associated complications [181].

PREVENTION — Modes of transmission are described above; issues related to prevention vary with mode of transmission as described in the following sections. (See 'Transmission' above.)

Preventive measures for pregnant and lactating women and women of childbearing potential are discussed separately. (See "Zika virus infection: Evaluation and management of pregnant patients", section on 'Prevention'.)

Mosquito protection — Individuals in areas with risk for transmission should take measures to avoid mosquito bites, including personal protection as well as environmental control measures [62]. Aedes mosquitoes bite during the daytime as well as at twilight; they breed in standing water (particularly manmade containers) [182].

Personal protective measures include [62,183-185]:

●Preventing mosquito bites by wearing long sleeves and long pants, using insect repellent, and staying indoors as feasible (with air conditioning, window/door screens, and/or mosquito nets to minimize contact between mosquitoes and people). (See "Prevention of arthropod and insect bites: Repellents and other measures".)

●Individuals with Zika virus infection may reduce spread of infection to others by following the same precautions to avoid mosquito bites during the first week of illness (the likely window of viremia).

●Asymptomatic individuals who have traveled to an area with Zika virus mosquito transmission and then return to an area with no Zika virus mosquito transmission should avoid mosquito bites for three weeks after return (the period during which they could become viremic).

Environmental control measures include identification and elimination of potential mosquito breeding sites. Mosquito larvae breed in standing water; therefore, residents should be instructed to avoid allowing standing water to collect outdoors (such as in flower pots, buckets, bottles, jars, and other similar containers near houses). Domestic water tanks should be covered so that mosquitoes cannot enter, and drains that allow stagnant or standing water should be eliminated. Local and district health departments can help facilitate mitigation of transmission risk. (See "Malaria: Epidemiology, prevention, and control", section on 'Mosquito control'.)

Sexual transmission — Sexual transmission has been described; the duration of viral persistence in semen and in female genital tract secretions may be prolonged. (See 'Transmission' above.)

In all areas, men or women with Zika virus infection or exposure (via travel to or residence in mosquito transmission areas, or unprotected sexual contact with an individual who has traveled to or resided in mosquito transmission areas) who have a pregnant partner should abstain from unprotected sex for the duration of the pregnancy [52]. (See "External (formerly male) condoms" and "Internal (formerly female) condoms".)

Within areas of Zika virus mosquito transmission, it is prudent for individuals to abstain from sexual activity (vaginal, anal, and oral sex) or use barrier protection while active transmission persists [186].

Outside areas of Zika virus mosquito transmission, we agree with guidance issued by the World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC) for couples where one or both partners have Zika virus infection or exposure, which include the following [52,187-190]:

●Men (whether symptomatic or not) should wait at least three months after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic) before unprotected sex.

●Women (whether symptomatic or not) should wait at least eight weeks after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic) before unprotected sex.

Issues related to prevention of Zika virus during pregnancy are discussed further separately. (See "Zika virus infection: Evaluation and management of pregnant patients", section on 'Prevention'.)

Blood/tissue donation — Zika virus is transmissible via blood products and organ or tissue transplantation [24,50]. Issues related to donor screening are discussed further separately. (See "Blood donor screening: Medical history", section on 'Zika virus' and "Blood donor screening: Laboratory testing".)

The US Food and Drug Administration (FDA) has issued donor deferral recommendations for hematopoietic stem cells, tissues, and donor gametes; the recommendations do not apply to solid organs [191]. Living donors with Zika virus infection or relevant epidemiologic exposure (residence in or travel to an area where mosquito-borne transmission of Zika virus infection has been reported, or unprotected sexual contact with a person who meets these criteria) should be considered ineligible for donation for six months. Deceased donors with Zika virus infection in the preceding six months should be also be considered ineligible.

Nosocomial transmission — Transmission of Zika virus via occupational exposure in a healthcare setting has not been described. Standard precautions are appropriate for protection of healthcare personnel and patients from Zika virus infection in these settings [186,192]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Standard precautions'.)

Vaccine development — Vaccine development is under way. Several inactivated vaccine candidates have been found to induce detectable neutralizing antibodies in phase I trials [193-195]. In one of the studies, serum from participants protected immunocompromised mice from developing disease after Zika virus challenge, indicating that vaccine-induced antibodies can prevent infection and disease in vivo [195]. The efficacy of vaccination in preventing human infection with Zika virus will need to be evaluated in an endemic region with a larger study population [196].

In a phase 1 trial of Ad26.ZIKV.001, an adenovirus vectored vaccine, 100 healthy volunteers were randomly assigned to receive vaccine (low dose followed by placebo, high dose followed by placebo, two low doses, or two high doses) or placebo [197]. Antibody responses up to one year after vaccination were observed in at least 80 percent of participants in both two-dose (high and low) groups, and a similar level of neutralizing antibody titers at one year was observed among those who received a single high-dose vaccine and those who received a two-dose regimen. All regimens were well tolerated; no safety concerns were identified. Further study is needed, including assessment in endemic areas among those individuals likely to become flavivirus exposed.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Zika virus infection".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Zika virus infection (The Basics)" and "Patient education: Guillain-Barré syndrome (The Basics)")

SUMMARY

●Epidemiology – Outbreaks of Zika virus infection have occurred in Africa, Southeast Asia, the Pacific Islands, the Americas, and the Caribbean. In 2015 and 2016, a Zika virus outbreak occurred in the Americas, the Caribbean, and the Pacific. Zika virus is transmitted to humans via the bite of an infected Aedes mosquito. This type of mosquito usually bites during the daytime and breeds in standing water (particularly manmade containers). (See 'Epidemiology' above.)

●Clinical manifestations – Clinical manifestations of Zika virus infection include acute onset of low-grade fever with maculopapular pruritic rash, arthralgia (notably in the small joints of the hands and feet), or conjunctivitis (nonpurulent); clinical illness is consistent with Zika virus disease if two or more of these symptoms are present. Zika virus infection has also been associated with congenital microcephaly, fetal loss, and Guillain-Barré syndrome. (See 'Clinical manifestations' above.)

●Clinical course – The incubation period between mosquito bite and onset of clinical manifestations is typically 2 to 14 days. The illness is usually mild; clinical manifestations usually resolve within two to seven days. Asymptomatic infection is common; symptoms develop in 20 to 25 percent of individuals who become infected with Zika virus. Once a person has been infected, he or she is likely to be protected from future infections. (See 'Symptoms and signs' above.)

●Diagnosis - The diagnosis of Zika virus infection should be suspected in individuals with typical clinical manifestations and relevant epidemiologic exposure (residence in or travel to an area where mosquito-borne transmission of Zika virus infection has been reported, or unprotected sexual contact with a person who meets these criteria). (See 'Diagnosis' above.)

The diagnosis of Zika virus infection is established via real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing for Zika viral RNA (in serum, urine, or whole blood) or serology. The approach to diagnostic testing depends on the timing of presentation after onset of symptoms (algorithm 1). (See 'Diagnosis' above.)

●Management – There is no specific treatment for Zika virus infection and there is no vaccine for prevention. Management consists of symptomatic treatment. Preventive measures include personal protective measures to prevent mosquito bites and institution of measures to eliminate and control mosquito breeding sites. (See 'Management' above and 'Mosquito protection' above.)

●Sexual transmission – Sexual transmission of Zika virus has been described. In all areas, men or women with Zika virus infection or exposure (via travel to mosquito transmission areas or sexual contact) who have a pregnant partner should abstain from unprotected sex for the duration of the pregnancy. Within areas of Zika virus mosquito transmission, it is prudent for individuals to abstain from sexual activity (vaginal, anal, and oral sex) or use barrier protection while active transmission persists. (See 'Sexual transmission' above.)

●Guidance for sexual activity – Outside areas of Zika virus mosquito transmission, guidance for couples where one or both partners have Zika virus infection or exposure include the following (see 'Sexual transmission' above):

•Men (whether symptomatic or not) should wait at least three months after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic) before unprotected sex.

•Women (whether symptomatic or not) should wait at least eight weeks after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic) before unprotected sex.

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  140. Oehler E, Watrin L, Larre P, et al. Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013. Euro Surveill 2014; 19.
  141. Cao-Lormeau VM, Blake A, Mons S, et al. Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 2016; 387:1531.
  142. Paploski IA, Prates AP, Cardoso CW, et al. Time Lags between Exanthematous Illness Attributed to Zika Virus, Guillain-Barré Syndrome, and Microcephaly, Salvador, Brazil. Emerg Infect Dis 2016; 22:1438.
  143. Krauer F, Riesen M, Reveiz L, et al. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review. PLoS Med 2017; 14:e1002203.
  144. Ikejezie J, Shapiro CN, Kim J, et al. Zika Virus Transmission - Region of the Americas, May 15, 2015-December 15, 2016. MMWR Morb Mortal Wkly Rep 2017; 66:329.
  145. da Silva IRF, Frontera JA, Bispo de Filippis AM, et al. Neurologic Complications Associated With the Zika Virus in Brazilian Adults. JAMA Neurol 2017; 74:1190.
  146. Styczynski AR, Malta JMAS, Krow-Lucal ER, et al. Increased rates of Guillain-Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil. PLoS Negl Trop Dis 2017; 11:e0005869.
  147. Salinas JL, Walteros DM, Styczynski A, et al. Zika virus disease-associated Guillain-Barré syndrome-Barranquilla, Colombia 2015-2016. J Neurol Sci 2017; 381:272.
  148. Dirlikov E, Medina NA, Major CG, et al. Acute Zika Virus Infection as a Risk Factor for Guillain-Barré Syndrome in Puerto Rico. JAMA 2017; 318:1498.
  149. Rozé B, Najioullah F, Fergé JL, et al. Guillain-Barré Syndrome Associated With Zika Virus Infection in Martinique in 2016: A Prospective Study. Clin Infect Dis 2017; 65:1462.
  150. Dirlikov E, Major CG, Medina NA, et al. Clinical Features of Guillain-Barré Syndrome With vs Without Zika Virus Infection, Puerto Rico, 2016. JAMA Neurol 2018; 75:1089.
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  152. Mécharles S, Herrmann C, Poullain P, et al. Acute myelitis due to Zika virus infection. Lancet 2016; 387:1481.
  153. Carteaux G, Maquart M, Bedet A, et al. Zika Virus Associated with Meningoencephalitis. N Engl J Med 2016; 374:1595.
  154. Rozé B, Najioullah F, Signate A, et al. Zika virus detection in cerebrospinal fluid from two patients with encephalopathy, Martinique, February 2016. Euro Surveill 2016; 21.
  155. Schwartzmann PV, Ramalho LN, Neder L, et al. Zika Virus Meningoencephalitis in an Immunocompromised Patient. Mayo Clin Proc 2017; 92:460.
  156. Galliez RM, Spitz M, Rafful PP, et al. Zika Virus Causing Encephalomyelitis Associated With Immunoactivation. Open Forum Infect Dis 2016; 3:ofw203.
  157. Zucker J, Neu N, Chiriboga CA, et al. Zika Virus-Associated Cognitive Impairment in Adolescent, 2016. Emerg Infect Dis 2017; 23:1047.
  158. Baud D, Musso D, Vouga M, et al. Zika virus: A new threat to human reproduction. Am J Reprod Immunol 2017; 77.
  159. Joguet G, Mansuy JM, Matusali G, et al. Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study. Lancet Infect Dis 2017; 17:1200.
  160. Sharp TM, Fischer M, Muñoz-Jordán JL, et al. Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses. MMWR Recomm Rep 2019; 68:1.
  161. Petersen EE, Staples JE, Meaney-Delman D, et al. Interim Guidelines for Pregnant Women During a Zika Virus Outbreak--United States, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:30.
  162. Centers for Disease Control and Prevention. Zika Virus: For Health Care Providers: Diagnostic Testing. http://www.cdc.gov/zika/hc-providers/diagnostic.html (Accessed on January 13, 2016).
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  164. Oduyebo T, Petersen EE, Rasmussen SA, et al. Update: Interim Guidelines for Health Care Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure - United States, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:122.
  165. Interim Guidance for Zika Virus Testing of Urine - United States, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:474.
  166. Rabe IB, Staples JE, Villanueva J, et al. Interim Guidance for Interpretation of Zika Virus Antibody Test Results. MMWR Morb Mortal Wkly Rep 2016; 65:543.
  167. Madad SS, Masci J, Cagliuso NV Sr, Allen M. Preparedness for Zika Virus Disease - New York City, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:1161.
  168. Announcement: Guidance for U.S. Laboratory Testing for Zika Virus Infection: Implications for Health Care Providers. MMWR Morb Mortal Wkly Rep 2016; 65:1304.
  169. St George K, Sohi IS, Dufort EM, et al. Zika Virus Testing Considerations: Lessons Learned from the First 80 Real-Time Reverse Transcription-PCR-Positive Cases Diagnosed in New York State. J Clin Microbiol 2017; 55:535.
  170. Tsai WY, Youn HH, Brites C, et al. Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests. Clin Infect Dis 2017; 65:1829.
  171. Centers for Disease Control and Prevention. New CDC Laboratory Test for Zika Virus Authorized for Emergency Use by FDA. http://www.cdc.gov/media/releases/2016/s0318-zika-lab-test.html (Accessed on March 21, 2016).
  172. Centers for Disease Control and Prevention. Questions and answers for obstetrical healthcare providers: Pregnant women and Zika virus infection. http://www.cdc.gov/zika/hc-providers/qa-pregnant-women.html (Accessed on February 02, 2016).
  173. US Food and Drug Administration. Emergency Use Authorizations. http://www.fda.gov/MedicalDevices/Safety/EmergencySituations/ucm161496.htm#zika (Accessed on May 02, 2016).
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  175. Centers for Disease Control and Prevention. CDC Health Alert Network (HAN) Health Update: CDC Recommendations for Subsequent Zika IgM Antibody Testing. https://content.govdelivery.com/accounts/USCDC/bulletins/150b812 (Accessed on June 23, 2016).
  176. US Food & Drug Administration. FDA Warns Health Care Providers Against Relying Solely on Zika Virus Serological IgM Assay Results; Reminds them to Wait for Confirmatory Test Results Before Making Patient Management Decisions: FDA Safety Communication. http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm534515.htm (Accessed on January 03, 2017).
  177. Villamil-Gómez WE, González-Camargo O, Rodriguez-Ayubi J, et al. Dengue, chikungunya and Zika co-infection in a patient from Colombia. J Infect Public Health 2016; 9:684.
  178. Waggoner JJ, Gresh L, Vargas MJ, et al. Viremia and Clinical Presentation in Nicaraguan Patients Infected With Zika Virus, Chikungunya Virus, and Dengue Virus. Clin Infect Dis 2016; 63:1584.
  179. Silva MMO, Tauro LB, Kikuti M, et al. Concomitant Transmission of Dengue, Chikungunya, and Zika Viruses in Brazil: Clinical and Epidemiological Findings From Surveillance for Acute Febrile Illness. Clin Infect Dis 2019; 69:1353.
  180. Centers for Disease Control and Prevention. Zika Virus: Symptoms, Diagnosis, & Treatment. http://www.cdc.gov/zika/symptoms/index.html (Accessed on January 13, 2016).
  181. World Health Organization. Emergencies preparedness, response: Psychosocial support for pregnant women and for families with microcephaly and other neurological complications in the context of Zika virus: Interim guidance for health-care providers. http://who.int/csr/resources/publications/zika/psychosocial-support/en/ (Accessed on February 29, 2016).
  182. Jansen CC, Beebe NW. The dengue vector Aedes aegypti: what comes next. Microbes Infect 2010; 12:272.
  183. Centers for Disease Control and Prevention. Interim Guidance for Protecting Workers from Occupational Exposure to Zika Virus. http://www.cdc.gov/niosh/topics/outdoor/mosquito-borne/pdfs/osha-niosh_fs-3855_zika_virus_04-2016.pdf#page=1 (Accessed on April 25, 2016).
  184. Centers for Disease Control and Prevention. Zika virus: Prevention. http://www.cdc.gov/zika/prevention/index.html (Accessed on June 08, 2016).
  185. LaRocque RL, Ryan ET. Personal Actions to Minimize Mosquito-Borne Illnesses, Including Zika Virus. Ann Intern Med 2016; 165:589.
  186. Müller JA, Harms M, Schubert A, et al. Inactivation and Environmental Stability of Zika Virus. Emerg Infect Dis 2016; 22:1685.
  187. Petersen EE, Polen KN, Meaney-Delman D, et al. Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure--United States, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:315.
  188. Petersen EE, Meaney-Delman D, Neblett-Fanfair R, et al. Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Persons with Possible Zika Virus Exposure - United States, September 2016. MMWR Morb Mortal Wkly Rep 2016; 65:1077.
  189. Polen KD, Gilboa SM, Hills S, et al. Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Men with Possible Zika Virus Exposure — United States, August 2018. MMWR Morb Mortal Wkly Rep 2018.
  190. World Health Organization 2020. WHO guidelines for the prevention of sexual transmission of Zika virus. file:///C:/Users/khall/Downloads/9789241550482-eng.pdf (Accessed on August 24, 2023).
  191. US Food and Drug Administration. Donor Screening Recommendations to Reduce the Risk of Transmission of Zika Virus by Human Cells, Tissues, and Cellular and Tissue-Based Products: Guidance for Industry, March 2016. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Tissue/UCM488582.pdf (Accessed on March 07, 2016).
  192. Olson CK, Iwamoto M, Perkins KM, et al. Preventing Transmission of Zika Virus in Labor and Delivery Settings Through Implementation of Standard Precautions - United States, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:290.
  193. Gaudinski MR, Houser KV, Morabito KM, et al. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials. Lancet 2017.
  194. Modjarrad K, Lin L, George SL, et al. Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials. Lancet 2018; 391:563.
  195. Tebas P, Roberts CC, Muthumani K, et al. Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine. N Engl J Med 2021; 385:e35.
  196. Durham DP, Fitzpatrick MC, Ndeffo-Mbah ML, et al. Evaluating Vaccination Strategies for Zika Virus in the Americas. Ann Intern Med 2018; 168:621.
  197. Salisch NC, Stephenson KE, Williams K, et al. A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study of Ad26.ZIKV.001, an Ad26-Vectored Anti-Zika Virus Vaccine. Ann Intern Med 2021; 174:585.
Topic 106169 Version 200.0

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46 : Revision to CDC's Zika Travel Notices: Minimal Likelihood for Mosquito-Borne Zika Virus Transmission at Elevations Above 2,000 Meters.

47 : Revision to CDC's Zika Travel Notices: Minimal Likelihood for Mosquito-Borne Zika Virus Transmission at Elevations Above 2,000 Meters.

48 : Revision to CDC's Zika Travel Notices: Minimal Likelihood for Mosquito-Borne Zika Virus Transmission at Elevations Above 2,000 Meters.

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54 : Zika virus in the female genital tract.

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61 : Outbreak of Zika Virus Infection, Chiapas State, Mexico, 2015, and First Confirmed Transmission by Aedes aegypti Mosquitoes in the Americas.

62 : Outbreak of Zika Virus Infection, Chiapas State, Mexico, 2015, and First Confirmed Transmission by Aedes aegypti Mosquitoes in the Americas.

63 : Detection of Zika virus in urine.

64 : Detection of Zika virus in saliva.

65 : Infectious Zika viral particles in breastmilk.

66 : Zika virus detection in urine from patients with Guillain-Barrésyndrome on Martinique, January 2016.

67 : Isolation of infectious Zika virus from saliva and prolonged viral RNA shedding in a traveller returning from the Dominican Republic to Italy, January 2016.

68 : Zika virus in the female genital tract.

69 : Zika virus genital tract shedding in infected women of childbearing age

70 : Evidence for Mother-to-Child Transmission of Zika Virus Through Breast Milk.

71 : Persistence of Zika Virus in Body Fluids - Final Report.

72 : Detection of Zika virus RNA in whole blood of imported Zika virus disease cases up to 2 months after symptom onset, Israel, December 2015 to April 2016.

73 : Prolonged Detection of Zika Virus in Vaginal Secretions and Whole Blood.

74 : Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities.

75 : Prolonged Zika Virus Viremia during Pregnancy.

76 : Prolonged Detection of Zika Virus Nucleic Acid Among Symptomatic Pregnant Women: A Cohort Study.

77 : Prolonged detection of Zika virus RNA in urine samples during the ongoing Zika virus epidemic in Brazil.

78 : Comparison of Test Results for Zika Virus RNA in Urine, Serum, and Saliva Specimens from Persons with Travel-Associated Zika Virus Disease - Florida, 2016.

79 : Persistent detection of Zika virus RNA in semen for six months after symptom onset in a traveller returning from Haiti to Italy, February 2016.

80 : Isolation of Infective Zika Virus from Urine and Saliva of Patients in Brazil.

81 : Kinetics of Zika Viral Load in Semen.

82 : Detection of Zika Virus in Semen.

83 : Zika virus in semen of a patient returning from a non-epidemic area.

84 : Sexual Transmission of Zika Virus and Persistence in Semen, New Zealand, 2016.

85 : Persistent Zika Virus Detection in Semen in a Traveler Returning to the United Kingdom from Brazil, 2016.

86 : Presence and Persistence of Zika Virus RNA in Semen, United Kingdom, 2016.

87 : Zika Virus Shedding in Semen of Symptomatic Infected Men.

88 : Late sexual transmission of Zika virus related to persistence in the semen.

89 : Probable sexual transmission of Zika virus from a vasectomised man.

90 : Persistence of Zika virus in conjunctival fluid of convalescence patients.

91 : Virus and Antibody Dynamics in Travelers With Acute Zika Virus Infection.

92 : Preliminary Findings from an Investigation of Zika Virus Infection in a Patient with No Known Risk Factors - Utah, 2016.

93 : Fatal Zika Virus Infection with Secondary Nonsexual Transmission.

94 : Fatal Zika Virus Infection with Secondary Nonsexual Transmission.

95 : Fatal Zika Virus Infection with Secondary Nonsexual Transmission.

96 : Fatal Sickle Cell Disease and Zika Virus Infection in Girl from Colombia.

97 : Clinical management of pregnant women exposed to Zika virus.

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99 : Zika virus associated deaths in Colombia.

100 : Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua.

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105 : Zika Virus Outbreak in Rio de Janeiro, Brazil: Clinical Characterization, Epidemiological and Virological Aspects.

106 : Mucocutaneous Findings and Course in an Adult With Zika Virus Infection.

107 : Cutaneous Eruption in a U.S. Woman with Locally Acquired Zika Virus Infection.

108 : Main Characteristics of Zika Virus Exanthema in Guadeloupe.

109 : Biphasic Zika Illness With Rash and Joint Pain.

110 : Biphasic Zika Illness With Rash and Joint Pain.

111 : Incidence and Outcome of Severe and Nonsevere Thrombocytopenia Associated With Zika Virus Infection-Puerto Rico, 2016.

112 : Zika virus infections imported to Italy: clinical, immunological and virological findings, and public health implications.

113 : Thrombocytopenia and subcutaneous bleedings in a patient with Zika virus infection.

114 : Uveitis Associated with Zika Virus Infection.

115 : Zika Virus Infection Associated With Severe Thrombocytopenia.

116 : Facial Puffiness in a Returning Traveler From Puerto Rico: Chikungunya, Dengue Fever, or Zika Virus?

117 : Bilateral posterior uveitis associated with Zika virus infection.

118 : Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016.

119 : Transient Hearing Loss in Adults Associated With Zika Virus Infection.

120 : Transient Myocarditis Associated With Acute Zika Virus Infection.

121 : Pericarditis Associated With Acute Zika Virus Infection in a Returning Traveler.

122 : Incidence and outcome of severe and non-severe thrombocytopenia associated with zika virus infection—Puerto Rico, 2016

123 : Association of Anterior Uveitis With Acute Zika Virus Infection in Adults.

124 : Zika Virus Infection and Solid Organ Transplantation: A New Challenge.

125 : Update: Interim Guidelines for Health Care Providers Caring for Infants and Children with Possible Zika Virus Infection--United States, February 2016.

126 : Characteristics of Children Aged<18 Years with Zika Virus Disease Acquired Postnatally - U.S. States, January 2015-July 2016.

127 : Characteristics of Zika Virus Disease in Children: Clinical, Hematological, and Virological Findings from an Outbreak in Singapore.

128 : Clinical Impact of Non-Congenital Zika Virus Infection in Infants and Children.

129 : Symptomatic Zika Virus Infection in Infants, Children, and Adolescents Living in Puerto Rico.

130 : Postnatally Acquired Zika Virus Disease Among Children, United States, 2016-2017.

131 : Postnatally Acquired Zika Virus Disease Among Children, United States, 2016-2017.

132 : Zika Virus Disease: A CDC Update for Pediatric Health Care Providers.

133 : Review: Evidence of Neurological Sequelae in Children With Acquired Zika Virus Infection.

134 : Neurologic Manifestations of Noncongenital Zika Virus in Children.

135 : Epilepsy surveillance in normocephalic children with and without prenatal Zika virus exposure.

136 : Dengue and Zika virus infections in children elicit cross-reactive protective and enhancing antibodies that persist long term.

137 : Guillain-BarréSyndrome During Ongoing Zika Virus Transmission - Puerto Rico, January 1-July 31, 2016.

138 : Zika Virus and the Guillain-BarréSyndrome - Case Series from Seven Countries.

139 : Guillain-BarréSyndrome Associated with Zika Virus Infection in Colombia.

140 : Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013.

141 : Guillain-BarréSyndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.

142 : Time Lags between Exanthematous Illness Attributed to Zika Virus, Guillain-BarréSyndrome, and Microcephaly, Salvador, Brazil.

143 : Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-BarréSyndrome: Systematic Review.

144 : Zika Virus Transmission - Region of the Americas, May 15, 2015-December 15, 2016.

145 : Neurologic Complications Associated With the Zika Virus in Brazilian Adults.

146 : Increased rates of Guillain-Barrésyndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil.

147 : Zika virus disease-associated Guillain-Barrésyndrome-Barranquilla, Colombia 2015-2016.

148 : Acute Zika Virus Infection as a Risk Factor for Guillain-BarréSyndrome in Puerto Rico.

149 : Guillain-BarréSyndrome Associated With Zika Virus Infection in Martinique in 2016: A Prospective Study.

150 : Clinical Features of Guillain-BarréSyndrome With vs Without Zika Virus Infection, Puerto Rico, 2016.

151 : Clinical Features of Guillain-BarréSyndrome With vs Without Zika Virus Infection, Puerto Rico, 2016.

152 : Acute myelitis due to Zika virus infection.

153 : Zika Virus Associated with Meningoencephalitis.

154 : Zika virus detection in cerebrospinal fluid from two patients with encephalopathy, Martinique, February 2016.

155 : Zika Virus Meningoencephalitis in an Immunocompromised Patient.

156 : Zika Virus Causing Encephalomyelitis Associated With Immunoactivation.

157 : Zika Virus-Associated Cognitive Impairment in Adolescent, 2016.

158 : Zika virus: A new threat to human reproduction.

159 : Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study.

160 : Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses.

161 : Interim Guidelines for Pregnant Women During a Zika Virus Outbreak--United States, 2016.

162 : Interim Guidelines for Pregnant Women During a Zika Virus Outbreak--United States, 2016.

163 : Interim Guidelines for Pregnant Women During a Zika Virus Outbreak--United States, 2016.

164 : Update: Interim Guidelines for Health Care Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure - United States, 2016.

165 : Interim Guidance for Zika Virus Testing of Urine - United States, 2016.

166 : Interim Guidance for Interpretation of Zika Virus Antibody Test Results.

167 : Preparedness for Zika Virus Disease - New York City, 2016.

168 : Announcement: Guidance for U.S. Laboratory Testing for Zika Virus Infection: Implications for Health Care Providers.

169 : Zika Virus Testing Considerations: Lessons Learned from the First 80 Real-Time Reverse Transcription-PCR-Positive Cases Diagnosed in New York State.

170 : Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests.

171 : Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests.

172 : Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests.

173 : Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests.

174 : Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests.

175 : Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests.

176 : Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests.

177 : Dengue, chikungunya and Zika co-infection in a patient from Colombia.

178 : Viremia and Clinical Presentation in Nicaraguan Patients Infected With Zika Virus, Chikungunya Virus, and Dengue Virus.

179 : Concomitant Transmission of Dengue, Chikungunya, and Zika Viruses in Brazil: Clinical and Epidemiological Findings From Surveillance for Acute Febrile Illness.

180 : Concomitant Transmission of Dengue, Chikungunya, and Zika Viruses in Brazil: Clinical and Epidemiological Findings From Surveillance for Acute Febrile Illness.

181 : Concomitant Transmission of Dengue, Chikungunya, and Zika Viruses in Brazil: Clinical and Epidemiological Findings From Surveillance for Acute Febrile Illness.

182 : The dengue vector Aedes aegypti: what comes next.

183 : The dengue vector Aedes aegypti: what comes next.

184 : The dengue vector Aedes aegypti: what comes next.

185 : Personal Actions to Minimize Mosquito-Borne Illnesses, Including Zika Virus.

186 : Inactivation and Environmental Stability of Zika Virus.

187 : Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure--United States, 2016.

188 : Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Persons with Possible Zika Virus Exposure - United States, September 2016.

189 : Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Men with Possible Zika Virus Exposure—United States, August 2018

190 : Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Men with Possible Zika Virus Exposure—United States, August 2018

191 : Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Men with Possible Zika Virus Exposure—United States, August 2018

192 : Preventing Transmission of Zika Virus in Labor and Delivery Settings Through Implementation of Standard Precautions - United States, 2016.

193 : Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials

194 : Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials.

195 : Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine.

196 : Evaluating Vaccination Strategies for Zika Virus in the Americas.

197 : A Double-Blind, Randomized, Placebo-Controlled Phase 1 Study of Ad26.ZIKV.001, an Ad26-Vectored Anti-Zika Virus Vaccine.

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